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United States Patent O??ce 1 3,069,316 Patented Dec. 18, 1962 2 active against the ?agellate Hexamita salmonis, the causa 3,069,316 tive organism of hexamitosis in trout and salmon. The previous known activity of fumagillin was against com Gilbert Fred Otto, Lake Bluff, Ill., assignor to ‘Abbott pletely unrelated protozoan organisms. It is effective against one amoeba organism Entamoeba histolytica in man, Nosema apis in bees but inactive against bacteria, fungi, viruses andv other closely related protozoa. More speci?cally, it has no activity against such pathogenic ?agellates as Trichomonas vaginalis, Trichomonas foetus, Trypanosoma gambiense and Spirochoeta vovyi. Thus, METHOD AND COMPOSITIONS FOR TREATMENT OF HEXAMETOSIS Laboratories, North Chicago, Ill., a corporation of Illinois No Drawing. Filed June 19, 1961, Ser. No. 117,216 6 Claims. (Cl. 167-53) This invention relates to a method and compositions for the treatment of ?sh disease and more particularly, it was most unexpected that fumagillin would be active it relates to compositions containing fumagillin and a against the related ?agellate, Hexamita salmonis. method for employing the same to treat trout and salmon Fumagillin is a well established antibiotic. It can be infected with hexamitosis. readily prepared as described in US. Patent 2,803,586 I-Iexamitosis is an enteric parasitic infection of trout 15 by fermenting Aspergillus fumigatus under submerged and salmon. The causative organism is a ?agellate aerobic conditions in a suitable nutrient medium and known as Hexamita salmonis. With the inevitable crowd isolating the fumagillin from the culture medium by ing of young ?sh in hatcheries, there is ample opportunity for massive exposure. Arti?cial conditions, including extraction with a suitable solvent. The method of treatment of the present invention in arti?cial feed, create various stress factors which in 20 volves incorporating fumagillin in pelletized ?sh feed and crease susceptibility to the infection. Mortality rates in providing these medicated pellets of feed to ?sh naturally hatcheries from the disease alone run as high as 50 to infected with hexamitosis for limited periods of time. 75% in young fry or ?ngerlings and on occasion newly in general, about 0.01 to 1.0% by weight of fumagillin hatched trout have been completely wiped out. In the in the diet is employed but about 0.2% by weight is past, mercurous chloride or p-ureidobenzenearsonic acid 25 preferable from the standpoint of effectiveness, toxicity have been employed in ?sh feed to treat the disease. and palatability. The continuous feeding of from 0.001 However, neither of these remedies is dependable or to about 0.002% by weight of fumagillin in the diet pro satisfactory. vides a good prophylactic practice for preventing hexami All species and varieties of trout and salmon appear to tosis infection in healthy trout and salmon. be susceptible to hexamitosis. It is usually evident as 30 In one test, fumagillin was incorporated in a concen~ chronic wasting disease, which runs its course in a matter tration of 0.2% by weight into a commercial trout feed of weeks accompanied by a high death rate. The ?sh containing meat meal, ground corn, soybean oil meal, fail to grow and lose weight. They are listless, often ?sh meal, dried buttermilk, brewer’s yeast and minor lying on the bottom and occasionally make quick spastic amounts of vitamins and essential minerals having an movements from side to side. Upon microscopic exami analysis of 56% protein, 4% fat and 5% ?ber. The nation, ?agellates are found in the intestinal contents of medicated feed was fed twice daily for ?ve days to 150 the sick ?sh. An acute outbreak of the disease may salmon ?ngerlings naturally infected with hexamitosis. become manifest only by the rapid death rate since 50% All of the treated salmon were completely free of para~ or more of the ?sh die within 24 to 48 hours of the ?rst sites at the end of the test period whereas the control sign of the disease. 40 group which was untreated was heavily infested with The problem of controlling hexamitosis is becoming more serious since trout hatcheries are rapidly increasing for the production of marketable ?sh and the stocking of fee ?shing ponds as well as the increasing amount of trout hatching by governmental agencies for stocking na tional waters for sport ?shermen. There are now about 150 large hatcheries in the United States alone and many smaller ones producing edible trout on a commercial basis. The development of pelletized dry ?sh feed in the past decade has accelerated the growth of the industry. Not less than 30,000 tons of such feed is currently sold annually ‘for trout and salmon raising. This market should double by 1965 and increase ten fold by 1975. As the trout industry grows, there will be increasing numbers of problems of disease control of which the most serious at present is hexamitosis. It would, therefore, be bene?cial to develop methods and compositions which are e?ective against this disease. parasites of Hexamita salmonis. In another test, fumagillin was fed to salmon infected with hexamitosis in a concentration of 1.0% of the feed as described above. Equally good results were obtained in that the treated ?sh were devoid of the parasites within 5 days While the untreated control group was heavily infested with parasites causing the disease. In still other tests, the parasite causing hexamitosis was completely eliminated from trout within 5 days or less when the ?sh were fed fumagillin in amounts rang ing from 0.01 to 0.04% by weight of their diet. A direct comparative study of fumagillin with mer curous chloride and p-ureidobenzenearsonic acid against hexamitosis in salmon ?ngerlings revealed that only fumagillin was effective in eliminating the infection at 0.2% by weight or less in the diet. There were no toxic effects upon the host even at a concentration of 1% by weight of the diet. In contrast, mercurous chloride was It is the main object of this invention to provide a completely inactive at 0.2% and toxic at 1.0% in the method for the treatment of hexamitosis in trout and 60 diet whereas p-ureidobenzenearsonic acid was e?ective at salmon. A further object is to provide compositions containing fumagillin which are very effective in eradicat ing hexamitosis in trout and salmon. It has now been discovered that fumagillin is extremely only 1% by weight in the diet. In similar tests, other antibiotics such as erythromycin and chlorotetracycline were ineffective against hexamitosis when employed at a concentration of 0.2% by weight in the diet of salmon. "8,069,316 ~ a 3 What I claim is: 1. A method‘ for treating salmon and trout to prevent and control hexamitosis which comprises feeding said ?sh a composition containing fumagillin. 4 5. A ?sh feed useful for the control of hexamitosis containing from 0.01 to 1% by weight of fumagillin. 6. In the practice of pisciculture, the method which comprises feeding ?sh a solid composition containing 2. A method as claimed in claim 1 in which the 5 from 0.001 to about 0.002% by weight of fumagillin to prevent hexamitosis. fumagillin is mixed with a solid carrier. 3. A method as claimed in claim 1 in which the fuma References Cited in the ?le of this patent gillin is present in an amount of from about 0.1% to 1% by weight of the composition. Lund: Yearbook of Agriculture 1956, pp. 444—446, 4. A method as claimed in claim 1 in which the fuma 10 US. G.P.O. gillin is present in an amount of about 0.2% by weight of the composition. Hussar: Antibiotics and Antibiotic Therapy, 1954, Macmillan C0., N.Y., pp. 377 and 378.